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Markers informative for ancestry demonstrate consistent megabase-length linkage disequilibrium in the African American population

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Abstract

Admixture mapping is a potentially powerful tool for mapping complex genetic diseases. For application of this method, admixed individuals must have genomes composed of large segments derived intact from each founding population. Such segments are thought to be present in African Americans (AA) and should be demonstrable by examination of linkage disequilibrium (LD). Previous studies using a variety of polymorphic markers have variably reported long-range LD or rapid decay of LD. To further define the extent and characteristics of LD caused by admixture in the AA population, the current study utilized a set of 52 diallelic markers that were selected for large standard variances between putative representatives of the founder populations. LD was examined in over 250 marker-pairs, including linked markers from four different chromosomal regions and an equal number of matched unlinked comparisons. In the representative founder populations, strong LD was not observed for markers separated by more than 10 kb. In contrast, results indicated significant LD (P<0.001, D′>0.3) in AA over large genomic segments exceeding 10 centiMorgans (cM) and 15 megabases (Mb). Only marginally significant LD was present between unlinked markers in this population, suggesting that choosing appropriate levels of significance for admixture mapping can minimize false positive results. The ability to detect LD for extended chromosomal segments in AA decayed not only as a function of the distance between markers, but also as a function of the standard variance of the markers. This examination of several genomic segments provides strong evidence that appropriate selection of informative markers is a crucial prerequisite for the application of admixture mapping to the AA population.

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Acknowledgements

Support for this research was provided by National Institutes of Health grants AR44804 and DK57249. The authors thank Yolanda Figueroa for assistance in application of computational algorithms and programs and Richard Cooper for providing anonymous African DNA samples.

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Authors and Affiliations

  1. Rowe Program in Human Genetics, Departments of Biological Chemistry and Medicine, University of California at Davis, One Shields Avenue, Davis, CA, 95616-8669, USA

    Heather E. Collins-Schramm, Bill Chima, Darwin J. Operario & Michael F. Seldin

  2. Rosalind Russell Medical Research Center for Arthritis, University of California, San Francisco, CA, 94143, USA

    Lindsey A. Criswell

Authors
  1. Heather E. Collins-Schramm
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  2. Bill Chima
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  3. Darwin J. Operario
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  4. Lindsey A. Criswell
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  5. Michael F. Seldin
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Corresponding author

Correspondence to Michael F. Seldin.

Electronic database information

Electronic database information

URLs for data in this article are as follows:

●:

US Census Bureau, http://www.census.gov (for size of the AA population)

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The SNP Consortium, http://snp.cshl.org/ (for initial screening information of the SNPs used in this study and other potential SNPs for admixture mapping)

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The Marshfield Center for Medical Genetics, http://research.marshfieldclinic.org/genetics (for initial screening information of the MIDs utilized in this study, including allele frequencies in several populations, and for cM positions)

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UCSC Human Genome Project Working Draft, http://genome.ucsc.edu/ (for Mb positions of MIDs)

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UC Davis, Rowe Program, http://roweprogram.ucdavis.edu/Seldin_lab_confidential/Linkage_Disequilibrium.pdf (for Web Table of all pairwise LD analyses in AA population)

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Collins-Schramm, H.E., Chima, B., Operario, D.J. et al. Markers informative for ancestry demonstrate consistent megabase-length linkage disequilibrium in the African American population. Hum Genet 113, 211–219 (2003). https://doi.org/10.1007/s00439-003-0961-1

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  • DOI: https://doi.org/10.1007/s00439-003-0961-1

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